Match Game Precision Cancer Medicine

Precision cancer medicine is moving into the clinic to identify the right drug for the right patient based on tumor genomics.

BY DARRELL E. WARD

“Precision cancer medicine” refers to a new standard of cancer care based on genomics that is making its way into the clinic.

“‘Precision’ refers to the use of genomic technologies that provide additional information to aid cancer diagnosis and treatment,” says Sameek Roychowdhury, MD, PhD, assistant professor of Medicine and of Pharmacology at The Ohio State University and member of the Translational Therapeutics Program at Ohio State’s Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

“Precision cancer medicine is already having a profound influence on clinical cancer care and clinical trial design, and it likely will move us away from the current organ-based classification of cancer to a molecular-based taxonomy,” says Roychowdhury, a specialist in clinical genomics for prostate cancer and other solid tumors.

The OSUCCC – James is both incorporating PCM in the clinic and advancing it through research.

The story of the epidermal growth factor receptor (EGFR) as a target of cancer therapy illustrates the development and advantages of PCM. By the late 1990s, clinical trials were under way to evaluate whether the drug gefitinib, designed to block EGFR signaling, was effective for non-small-cell lung cancer (NSCLC).

Gefitinib was the first of the EGFR inhibitors (erlotinib soon followed).

“The original gefitinib trials tested all patients with non-small-cell lung cancer, and the results were mildly encouraging,” Roychowdhury says. “About 10 percent of American patients with NSCLC responded quickly with stabilized disease and other partial responses, while other patients showed little or no response.” In Japan, a gefitinib trial showed 27 percent of patients experienced partial responses.

The drug seemed moderately promising. Afterward, two separate research groups sequenced EGFR genes from patients in the two trials to investigate why some patients responded better than others. The two groups reported their results simultaneously in 2004, one group in the New England Journal of Medicine, the other in the journal Science.

The findings were identical: Patients who responded to gefitinib had specific mutations in the EGFR gene. The results suggested that screening patients for EGFR mutations might identify which patients had gefitinib-sensitive tumors.

“The hypothesis that EGFR mutations played a role in gefitinib activity was there at the time, but those original trials were done before we could test patients in advance,” Roychowdhury says.

“In 2000, we lacked the understanding of new genetic alterations that are important for cancer and for drug development, and we lacked the technology to test large numbers of genes in individual patients,” he says.

“Today, we can sequence hundreds of genes for under $5,000, which enables us to look at the scope of all the genes we currently think are clinically important in cancer. Testing patients for EGFR mutations is now standard in the OSUCCC – James lung-cancer clinic.”